Foreman et al., U.S. Pat. No. 4,931,447, disclose (8.beta.)-N-cycloalkyl-1-alkyl-6-(substituted)ergoline-8-carboxamides of the formula ##STR1## wherein: R.sup.1 is a C.sub.1 -C.sub.4 alkyl;
R.sup.2 is allyl or C.sub.1 -C.sub.4 straight chain alkyl; PA1 R.sup.3 is hydrogen or C.sub.1 -C.sub.4 straight chain alkyl; PA1 R.sup.4 is hydrogen, C.sub.1 -C.sub.4 alkyl, hydroxy or C.sub.1 -C.sub.4 alkoxy; PA1 n is 0, 1, 2 or 3; and PA1 R.sup.2 is allyl or C.sub.1 -.sub.4 straight chain alkyl; PA1 R.sup.3 is hydrogen or C.sub.1 -C.sub.4 straight chain alkyl; PA1 R.sup.4 is pyridinyl or imidazolyl; PA1 alkyl is a divalent organic radical derived from a straight or branched C.sub.1 -C.sub.5 alkane; and the pharmaceutically acceptable acid addition salts thereof. Such reference compounds are said to be useful for blocking 5HT.sub.2 receptors in mammals having an excess of serotonin centrally or peripherally and, as such, are useful for-treating the disease states noted above. PA1 R.sup.2 and R.sup.3 are hydrogen, methyl, ethyl, propyl, isopropyl, phenyl or halophenyl; PA1 R.sup.4 is hydrogen, an aliphatic radical containing 1 to 3 carbon atoms or halo, or R.sup.3 and R.sup.4, when taken together, represent a C.sub.3 -C.sub.4 alkylene chain which together with the carbon atoms to which they are attached form a cycloaliphatic ring. The reference compounds are said to exhibit hypotensive and antiulcer activity. PA1 R.sup.2 is allyl or C.sub.1 -C.sub.4 alkyl; PA1 B is ##STR5## n is 0, 1 or 2; m is 1, 2, 3, 4 or 5; ##STR6## R.sup.3 and R.sup.4 are each independently hydrogen or C.sub.1 -C.sub.4 alkyl; PA1 Z is C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.8 cycloalkyl; and PA1 the pharmaceutically acceptable acid addition salts thereof.
the pharmaceutically acceptable acid addition salts thereof. The reference compounds are said to be useful for blocking 5HT.sub.2 receptors in mammals having an excess of serotonin centrally or peripherally and, as such, are useful for treating hypertension, migraine, vasospasm, thrombosis, ischemia, depression, anxiety, sleep, appetite disorders, and the like.
Cohen et al., U.S. Pat. No. 4,902,691, disclose (8.beta.)-N-heteroalkyl-1-alkyl-6-(substituted)ergoline-8-carboxamides of the formula ##STR2## wherein R.sup.1 is a C.sub.1 -.sub.4 alkyl;
Garbrecht et all., U.S. Pat. No. 3,183,234, disclose octahydroindoloquinolines of the formula ##STR3## wherein: R.sup.1 is hydrogen, methyl, ethyl, isopropyl, allyl or propargyl;
Despite the progress of science as represented above, many mammals, both humans and animals, continue to be afflicted with one or more of the disease states noted above. Accordingly, the need continues for safer, more selective- drugs which can be used to treat such diseases.
As such, an object of the present invention is to provide substituted cyclo or bicycloalkylamides of (8.beta.)-6-(substituted) ergolines which are useful for occupying the 5HT.sub.2 or 5HT.sub.1c receptors in mammals. Such activity renders the present compounds useful for treating disease states such as obesity, appetite disorders (such as bulemia) , obsessive-compulsive disorders, alcoholism, pain, sleep disorders ( such as sleep apnea), substance abuse, hypertension, thrombosis, bladder dysfunction, complications arising from atherosclerosis, migraine, vascular occlusive disease, vasospasm (both coronary and cerebral), ischemia, depression, anxiety, schizophrenia, sexual dysfunction and the like.